Efforts to induce antipsychotic activity with dopamine autoreceptor agonists have been successful (Dorsini I Adv. Biochem. Psychopharmacol., 16, 645-648, 1977; Tamminga et al., Science, 200, 567-568, 1975; and Tamminga et al., Psychiatry, 398-402, 1986). A method for determining intrinsic activity at the dopamine D.sub.2 receptor was recently reported (Lahti et al., Mol. Pharm., 42, 432-438, 1993) Intrinsic activity is predicted using the ratio of the "low-affinity agonist" (LowAg) state of the receptor and the "high-affinity agonist" (HighAg) state of the receptor, i.e. LowAg/HighAg. These ratios correlate with the agonist, partial agonist, and antagonist activities of a given compound, which activities characterize a compounds ability to elicit an antipsychotic effect.
In accordance with this invention, there is provided a group of compounds which are useful antipsychotic agents. The compounds of this invention are dopamine agonists various degrees of intrinsic activity some of which are selective autoreceptor agonists, and therefore partial agonist (i.e. activate only autoreceptors versus postsynaptic D.sub.2 dopamine receptors). As such, they provide functional modulation of the dopamine systems of the brain without the excessive blockade of the postsynaptic dopamine receptors which have been observed to be responsible for the serious side effects frequently exhibited by agents found otherwise clinically effective for the treatment of schizophrenia. Activation of the dopamine autoreceptors results in reduced neuronal firing a well as inhibition of dopamine synthesis and release and therefore provide a means of controlling hyperactivity of the dopaminergic systems. The compounds of this invention were also found to have high intrinsic activity and therefore they can behave as the natural neurotransmitter i.e. as full agonists. As such, they are useful in the treatment of diseases having abnormal concentrations of dopamine could be used as dopamine surrogates possibly in the treatment of Parkinson's disease. The compounds of this invention are essentially free from extrapyramidal side effects (EPS).